The present invention relates to methods for the treatment of tumors in mammals by injecting or infusing an effective anti-tumor amount of radiohalogenated pyrimidine nucleosides such as 5-halo 2'-deoxypryimidine and typically 5-iodo-2'-deoxyuridine in a pharmaceutically acceptable vehicle directly to the affected site. These nucleosides include for example, 5-.sup.123 I /.sup.125 I]iodo-2'-deoxyuridine which are hereinafter abbreviated as .sup.123 IUdR or .sup.125 IUdR.
The present invention also includes within its scope methods for diagnosing tumors and or predicting their progress by intratumor administration of .sup.123 IUdR or .sup.125 IUdR.
It has been demonstrated that the Auger effect accompanying the decay of iodine-125[.sup.125 I] or iodine-123[.sup.123 I] is extremely toxic to cultured mammalian cells when these are incorporated into nuclear DNA in the form of the corresponding thymidine analog i.e., 5-[.sup.123 I/.sup.125 I]iodo-2'-deoxyuridine [.sup.123 /.sup.125 IUdR]. Further in vitro studies indicated that these and other Auger electron emitters have also shown the ineffectiveness of this decay mode when it occurs at a distance from the nuclear DNA.
Tumors of the central nervous system are estimated to cause the death of 90,000 patients in the United States each year. One-fourth of the annual 4 billion dollar cost for care of cancer patients in the United States is allocated for patients inflicted with such neoplasms. The incidence of secondary neoplasms is much greater than that of primary neoplasms. In the young patient [3-12 years], CNS tumors comprise the most common group of solid tumors and account for 20% of all pediatric neoplasms. These tumors are different in histology and behavior from those seen in adults [50-70 years].
Gliomas comprise about 60% of all primary CNS tumors and they constitute the bulk of the intrinsic intraparenchymal tumors of both brain and spinal cord. These tumors arise from distinct types of glial cells. Regardless of the location of the malignant glioma, the prognosis has not changed greatly in the last 20 years. Following treatment, recurrence is usually observed within 6 months and 80% of these patients die within 6 to 12 months. Efforts to improve prognosis for this malignancy have included, among others, the development of microsurgical techniques; improvement in drug delivery systems; high dose radiotherapy alone or in combination with nitrosoureas such as N,N-bis(2-chloroethyl)-N-nitrosourea [BCNU]; radiotherapy trials of implanted radiation sources [brachytherapy] with seeds of iodine-125, iridium-192, or gold-198; local arterial infusions of BCNU or cisplatin; intrathecal administration of chemotherapeutic agents; use of interferon; administration of radiosensitizers such as IUdR and bromodeoxyuridine [BrUdR]; and most recently the use of .sup.131 I-labeled m-iodobenzylguanidine. Despite these therapeutic approaches, progress in the therapy of high-grade brain tumors, particularly glioblastoma multiform, has been modest at best. The fundamental problem lies in the impossibility of total removal or effective sterilization e.g., radiation, chemotherapy, etc. of the tumor. This impass motivates the search for alternate treatment modalities that will show preferential uptake and selective killing of these tumors.
For a number of years, the scientific and medical communities have been continually exploring the possibility of using radionuclides for cancer therapy. The use of sealed radioactive sources [e.g., radium needles and capsules] is now commonplace. However, with the exception of a select number of applications, the hopes of employing unsealed sources for the radiotherapy of a neoplastic disease remain largely unrealized. The problem has two components: (a) the paucity of appropriate radionuclides, and (b) the scarcity of carrier molecules that can (i) bring the radionuclide into the vicinity of cancerous cells and (ii) achieve high therapeutic ratios between tumor cells and normal tissues.